tbuckley/cabot-search huggingface dataset:
Abstract 14503: Cardiac Arrest Secondary to Inferior ST-Segment Elevation Myocardial Infarction in Patient With Paroxysmal Nocturnal Hemoglobinuria and COVID 19 Infection
Authors: Mohamed Salah Mohamed, Amr Salama, Anas Hashem, Ahmed Hussein, Mallory Balmer-Swain
Journal: Circulation (2022)

Background: Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) have attacks of complement-mediated hemolysis that can be spontaneous or secondary to precipitating factors such as infections. During these episodes, these patients have an increased risk of thrombosis, typically venous and rarely arterial. We present a rare case of cardiac arrest due to ventricular fibrillation (VF) and inferior STEMI in a patient with PNH and a recent COVID infection. Case: 63 years old male patient with a medical history of PNH presented with typical chest pain, fever, cough, jaundice, and dark-colored urine. On examination, he was hemodynamically stable with jaundiced eyes. A few minutes later, he had cardiac arrest due to VF. He achieved return of spontaneous circulation (ROSC) after two defibrillation shocks. EKG showed inferior STEMI. Labs showed hemoglobin of 6.4 g/dl, elevated cardiac markers, serum LDH, and indirect bilirubin. Serum haptoglobin was &lt; 1 mg/dl. His COVID 19 PCR test was positive. Decision making: He received 2 units of packed RBCs and underwent a coronary angiogram (CA) which revealed total proximal occlusion of the right coronary artery (Figure A). He underwent successful PCI by two drug-eluting stents (figure B). His peripheral blood immunophenotyping and flow cytometry was positive for loss of glycosylphosphatidylinositol-linked antigens and decreased expression of CD 59/14/24. He was started on Ravulizumab, a humanized monoclonal antibody complement five inhibitor. Conclusion: PNH and COVID increase the risk of thrombosis. Thrombosis mechanism in PNH includes platelets and coagulation system activation via complement cascade and impairment of the fibrinolytic system. COVID infection increases the risk of thrombosis by endothelial cell dysfunction and release of cytokines. Due to the patient’s acute presentation, he needed to undergo immediate CA and lifesaving PCI regardless of his hematological disorder or active COVID-19 infection.
Abstract 15217: Intrahepatic Gene Expression Profile Differences in Patients With Fontan Associated Liver Disease
Authors: Katia M Bravo Jaimes, Xiuju Wu, Leigh C Reardon, Gentian Lluri, Bita Naini, Kristina I Bostrom, Jamil A Aboulhosn, Fady Kaldas
Journal: Circulation (2022)

Introduction: Fontan associated liver disease (FALD) develops shortly after the Fontan palliation as the long-term consequence of chronically elevated central venous pressures. The molecular pathways underlying FALD remain largely unknown. We aimed to assess intrahepatic gene expression profile differences among these patients with advanced vs early fibrosis. Hypothesis: Advanced fibrosis in patients with Fontan circulation shows a specific gene expression profile with specific enriched pathways. Methods: This retrospective cohort study included adults with the Fontan circulation who had tissue available from at least one liver biopsy at the UCLA Adult Congenital Heart Disease Center. Clinical, laboratory, imaging and hemodynamic data prior to the liver biopsy were extracted from medical records. Patients were classified into early (F1-F2) or advanced fibrosis (F3-F4). RNA was isolated from formalin-fixed paraffin embedded liver tissue, RNA libraries were constructed using ribosomal RNA depletion method and sequencing was performed on Illumina Novaseq 6000. Differential gene expression and gene ontology analyses were carried out using DESeq2 and Metascape. Results: Seventy-seven patients were included, 53% women, 50% White and 20% Hispanic. Most patients had either a lateral tunnel (40%) or atriopulmonary (24%) Fontan. Four patients had 2 liver biopsies and 1 had hepatocellular carcinoma. Early and advanced fibrosis were present in 43 (54%) and 37 (46%) samples, respectively. Both groups had similar age, comorbidities, NYHA class, liver function tests and liver ultrasound features. Patients with advanced fibrosis had higher BNP, Fontan, mean pulmonary artery and capillary wedge pressures. Samples with advanced fibrosis had 921 up-regulated genes compared to the ones with early fibrosis. The up-regulated genes were enriched in extracellular matrix organization, regulation of cell adhesion, response to wounding, TGF-beta signaling pathway and blood vessel morphogenesis. Conclusions: Advanced fibrosis in patients with Fontan circulation exhibits up-regulated genes compared to early fibrosis, including pathways related to inflammation, congestion and angiogenesis, adding further insight into FALD pathophysiology.
Abstract 147: Volunteer Responders Often Provide Emotional Support To Relatives Of Out-of-hospital Cardiac Arrest Patients Even After Arrival Of The Emergency Medical Services
Authors: Astrid Rolin Kragh, Mads Christian Tofte Gregers, Anne Juul Grabmayr, Julie S Kjoelbye, Louise K Jakobsen, Linn Andelius, Fredrik Folke, Carolina Malta Hansen
Journal: Circulation (2022)

Introduction: Volunteer responders (VR) are dispatched to OHCA to fetch an AED and provide CPR. However, often more than one volunteer responder arrives, allowing additional responders to handle tasks beyond resuscitative efforts. We aimed to assess which tasks dispatched VR performed during resuscitation attempts and the proportion of VR providing emotional support to patient relatives. Method and Results: This was an observational study with prospectively collected data from Denmark's national volunteer responder cohort between April 2020 and May 2022. We included 18,489 VR who accepted an alarm and arrived at a presumed cardiac arrest. All VR who received an alarm received a survey 90 minutes after, which included questions regarding their handling of tasks (response rate 86.1%). Of 18,489 volunteers, 6,612 (35.8%) arrived before EMS. Among all VR who arrived at the cardiac arrest scene, 3,424 (18.5%) performed CPR, 1,851 (10.0%) attached an AED, and 3,447 (18.6%) provided support for relatives. In univariate logistic regression models, VR provision of CPR was significantly associated with being healthcare educated (OR: 1.76, 95% CI: 1.61-1.93), police or firefighter (OR: 3.28, 95% CI: 2.96-3.64). Further, odds for CPR provision increased with recent CPR course (OR: 2.48, 95% CI: 2.09-2.93). VR provision of CPR was significantly associated with an increasing number of VR arriving before EMS. Odds for the provision of CPR were doubled in cases where three or more VR arrived before EMS (OR:6.06, 95% CI: 5.29-6.94) compared to cases where one VR arrived (OR: 3.15, 95% CI: 2.70-3.69). When VR arrived after EMS, 14.9 % provided support for relatives (Fig 1). Conclusion: Volunteer responders’ engagement in OHCA is associated with educational background and the number of volunteers arriving before EMS. Provision of support for relatives is the most frequently handled task, even at arrival after the EMS.
Abstract 15164: Refractory Shock Following Ingestion of Gamma Hydroxy Butyrate Laced With Xylazine
Authors: Ammar Hasnie, Sebastian Schormann, Lauren V Daley, Jordan Minish, Reed Lahaye, Stefanie Krick
Journal: Circulation (2022)

Case: A 35 year old male with a complex psychiatric history including previous suicide attempts was brought to the emergency department after being found on a sidewalk with bradycardia and bradypnea by emergency medical services (EMS). He responded to naloxone administered by EMS and admitted to using heroin, gamma hydroxyl butyrate (GHB), and rohypnyol prior to becoming unconscious. On arrival, his vitals showed a sinus heart rate at 60, decreased respiratory rate with normal oxygenation, hypotension with systolic blood pressures in the 50’s, and hypothermia with a temperature of 95 degrees Fahrenheit. On physical exam his heart rate and rhythm were regular, lungs were clear to auscultation, he had pinpoint pupils, and was perfusing his extremities well with normal capillary refill without diaphoresis. A bedside echocardiogram showed normal left ventricular ejection fraction without signs of cardiogenic shock. He was subsequently started on two pressors but continued to clinically worsen requiring overmaxed doses of five pressors including Angiotensin II. He continued to clinically decline with worsening renal failure requiring CRRT therapy and remains ventilator dependent. Discussion: This patient was admitted to the intensive care unit for profound vasoplegic shock. The etiology of his shock was due to a veterinary drug called xylazine. Xylazine is a horse tranquilizer which is commonly laced in drugs of abuse including GHB. It’s an alpha 2 agonist which causes decreased sympathetic outflow and decreased norepinephrine release leading to a clinical presentation including profound hypotension, bradycardia, CNS depression, and miosis. While it can mimic opioid toxicity patients tend to have preserved respiratory status and transiently respond to painful stimulation. Patients who don’t concomitantly use opioids, do not typically respond to naloxone. It is critical to consider this in the differential in patients with an opioid toxidrome who don’t respond to naloxone. The treatment for xylazine overdose is supportive care of their hemodynamics. The half-life of the drug is around 48 hours but can persist for several days. While xylazine overdose generally carries a good prognosis, it can still lead to devastating consequences.
Abstract 14602: Does Cancer Treatment Break Your Heart? A Linked Health Data Analysis of Thecharacteristics and Survival of Patients Who Have Developed Cardiovascular Disease Post Cancer Treatment
Authors: Robyn A Clark, Saifei Lui
Journal: Circulation (2022)

Background: Cancer treatment induced cardiotoxicity, can be a devastating outcome of cancer therapy. It is possible that a patient can survive cancer but develop cardiovascular disease (CVD). Aim: to determine whether there are differences in the characteristics of cancer patients who received potentially cardiotoxic cancer therapy and subsequently developed CVD and those who did not. Methods: This epidemiological study will comprise a retrospective analysis of de-identified linked health data sets, including the Integrated Activity Collection (ISAAC) of Hospital Separations, South Australian Cancer Registry (SACR), Northern Territory Cancer Registry (NTCR) and mortality (Births Deaths and Marriage Registry Data) and NT Hospital Separation data. The total population will be segregated in two distinct groups namely ‘Cancer with no HF’ and ‘Cancer with HF’ to compare the between group differences by demographic factors and medical history. Results: Of the (n=17,389) patients who received chemotherapy cancer treatment between July 2001-June 2017, 49% (8,530) were diagnosed with HF post cancer treatment( median age at cancer diagnosis 65 years; 58% male); crude mortality was 73% within the HF and cancer group; cause of death within this group was HF related 14%; cancer related 63%; other 22% compared to the non HF and cancer group ( median age at cancer diagnosis 58 years; 53% male) who had a mortality rate of 46%; 6.2% CVD related; 68.8% cancer related and 25% other. Conclusion: After adjusting for age, sex, tumour grade, cancer site and CVD admissions prior to cancer diagnosis patients with CVD and cancer had poorer outcomes.
Abstract 15653: Impact of Atrial Fibrillation on Hospital Outcomes Among Covid-19 Patients - Insight From the 2020 California State Inpatient Database
Authors: Joseph A Salami, Muni Rubens, BENJAMIN A PATRICK, Anshul Saxena, Emir Veledar, Khurram Nasir
Journal: Circulation (2022)

Introduction: Recent estimates of COVID-19 in the US include over 84 million cases with over 1 million deaths. The association between new-onset atrial fibrillation (AF) and COVID-19 has been reported, but hospital outcomes has not been studied among COVID-19 patients with AF. Hypothesis: AF among COVID-19 hospitalizations is not associated with higher rates of adverse in-hospital outcomes. Methods: Using data from the 2020 California State Inpatient Database, we conducted a retrospective analysis of all hospitalized COVID-19 patients ≥18 years of age. Primary outcomes were: prolonged length of stay (LOS) [defined as LOS ≥75th percentile of the population], ICU admission, mechanical ventilation, vasopressor use, and in-hospital mortality. We examined the differences in adverse hospital outcomes among those with AF versus those without. Multivariate logistic regression analyses were used to estimate the association between AF and outcomes after adjusting for cofactors. Results: Our analysis had a total of 94,114 COVID-19 hospitalizations and 9,391 (10.0%) had AF. Adverse hospital outcomes such as prolonged LOS (40.0% versus 27.1%, P &lt;0.001), ICU admission (18.4% versus 8.8%, P &lt;0.001), mechanical ventilation (19.0% versus 9.1%, P &lt;0.001), vasopressor use (4.4% versus 1.9%, P &lt;0.001), and mortality (27.2% versus 9.6%, P &lt;0.001) were significantly higher among COVID-19 hospitalizations with AF. The adjusted odds ratio (aOR) of adverse outcomes such as prolonged LOS (aOR, 1.37, 95% CI: 1.31-1.44), ICU admission (aOR, 2.01, 95% CI: 1.88-2.15), mechanical ventilation (aOR, 1.95, 95% CI: 1.72-2.20), vasopressor use (aOR, 1.98, 95% CI: 1.86-2.11), and mortality (aOR, 2.04, 95% CI: 1.92-2.16) were statistically significantly higher among COVID-19 hospitalizations with AF compared to those without AF. Conclusions: In 2020, AF occurred in about 10% of COVID-19 hospitalizations in California, USA, and was associated with significantly greater risk of adverse hospital outcomes and mortality. COVID-19 patients should be closely monitored for development of AF, and promptly managed like contemporary AF. More studies are however needed to understand the best approach to managing AF in COVID-19 patients.
Abstract 15035: LIN28a Extends Regenerative Window of the Postnatal Heart and Promotes New Myocyte Formation in the Adult Heart After Injury via Lncrna-h19
Authors: Vagner O Rigaud, Robert Hoy, Justin Kurian, Clare Zarka, Michael Behanan, Isabella Brosious, Jennifer Pennise, Tej Patel, Lindsay Kraus, Sadia Mohsin, Steven R Houser, Mohsin Khan
Journal: Circulation (2022)

The neonatal heart holds a remarkable regenerative capacity that is lost within the first week of life coinciding with a profound shift in cardiomyocyte (CM) metabolism, and CM cell cycle arrest. Whether reprogramming metabolism reactivates CM cell cycle enhancing cardiac function and repair after injury is unknown. Here, we identify a novel role for the RNA-binding protein LIN28a, a master regulator of cellular metabolism, in cardiac development and repair following injury. LIN28a was found as primarily active during cardiac development and rapidly decreases after birth. Injury to the neonatal heart, but not in adults, reactivates LIN28a leading to regenerative processes while LIN28a inhibition with small molecules attenuated pro-reparative effects of the postnatal heart. LIN28a reintroduction at P1, P3, P5, P7, and P14 decreased maturation-associated polyploidization, nucleation, and cell size, enhancing CM cell cycle activity and number of CMs per hearts in LIN28a transgenic pups compared to WT littermates. Moreover, LIN28a overexpression extended CM cell cycle activity and regenerative processes beyond P7 resulting in increased cardiac function 30 days after apical resection. In the adult heart, LIN28a overexpression promoted formation of new CMs and enhanced cardiac function, and survival in mice 12 weeks after myocardial infarction compared to WT littermate controls. Furthermore, the percentage of mononucleated CMs in the LIN28a overexpressing hearts was positively correlated to better cardiac functional recovery after injury. Mechanistically, CMs overexpressing LIN28a showed increased glycolytic metabolism while its attenuation by 2-DG reverted LIN28a-induced enhancement in CM cell cycle activity in adult hearts 4 days after injury. LIN28a immunoprecipitation followed by RNA sequencing in CMs isolated from LIN28a injured hearts identified lncRNA-H19 as its most significantly altered target. Ablation of lncRNA-H19 blunted LIN28a-induced enhancement on CM metabolism and cell cycle activity. Collectively, LIN28a reprograms CM metabolism enhancing cell cycle activity in the injured heart and pro-reparative processes thereby linking CM metabolism to the regulation of ploidy/nucleation and repair in the heart.
Abstract 15165: Dobutamine Stress Echocardiography in Patients With Low Flow, Low Gradient Aortic Stenosis and Preserved Lvef
Authors: Nils Sofus Borg S Mogensen, Rasmus Carter-Storch, Mohamed-salah Annabi, Jasmine Grenier-Delaney, Jacob Moller, Kristian Altern Ovrehus, Philippe Pibarot, Marie-Annick A Clavel, Jordi Sanchez Dahl
Journal: Circulation (2022)

Introduction: Guidelines recommend the use of Dobutamine stress echocardiography (DSE) in case of low flow low gradient aortic stenosis (LFLG AS) when left ventricular ejection fraction (LVEF) &lt;50%, but few data support this threshold as most studies have tested DSE when LVEF &lt;35%. Hypothesis: To examine the feasibility of DSE in patients with LFLG AS, and the possible interaction between LVEF and accuracy of projected aortic valve area (AVA proj ) in correctly classifying severe AS defined by Cardiac Computer Tomography (C-CT). Methods: Patients with LFLG AS (aortic mean gradient &lt;40 mmHg &amp; AVA &lt;1.0 cm 2 &amp; stroke volume index (SV i ) &lt;35ml/m 2 ) undergoing DSE were identified from two prospective cohorts, and stratified according to LVEF (&lt;35%, 35-50% and &gt;50%). Severe AS was defined as AVC score ≥2000 AU in males, and ≥1200 AU in females on C-CT. Results: Of 214 patients, 65 (30%) presented with LVEF &lt;35%, 58 (27%) with LVEF 35-50%, and 91 (43%) with LVEF &gt;50%. 97 patients presented with severe AS (32 vs 21 vs 44, p=0.26). An inverse relationship was seen between LVEF and left ventricular diameter (60±10mm vs 54±7mm vs 47±6mm, p&lt;0.01). Although resting SV i was different between groups (26.4±6.4mL vs 27.3±5.6 vs 29.6±5.7, p&lt;0.01), no significant differences in SV i change was seen during DSE (7.3±5.9mL vs 5.5±6.2mL vs 6.7±6.7mL, p=0.30), and patients with LVEF &lt;35% were more likely to demonstrate flow-reserve, defined as an increase in SVi &gt;20%; 39 (63%) vs 21 (36%) vs 44 (49%), p=0.01. AVA proj provided similar AUCs (p=0.31) (Figure 1) and cut-off points in classifying severe AS across LVEF groups: LVEF&lt;35%: 1.02 cm 2 /accuracy 74%, vs LVEF 35-50%: 0.82cm 2 /accuracy 72% vs LVEF &gt;50%: 0.9cm 2 /accuracy 65%. Conclusion: DSE leads to similar increases in stroke volume index (SV i ) in patients with LVEF &gt;50% compared with LVEF ≤50%. Furthermore, the projected aortic valve area (AVA proj ) provides good accuracy for identification of true-severe AS, regardless of LVEF stratum.
Abstract 15027: Senescence-Associated Pathway Activation in Cardiac Fibroblasts in Dilated Cardiomyopathy
Authors: Andrew Antolic, Yoon J Shin, Jennifer M Kleinhenz, Zhe Jiao, Louise A Hecker, Michael A Burke
Journal: Circulation (2022)

Introduction: Cardiac fibrosis is a pathologic driver in heart failure (HF) and aging is a major risk factor for HF. Persistence of activated myofibroblasts is a key feature of pathological fibrosis. In an aging model of lung fibrosis, senescent myofibroblasts exhibit apoptosis-resistance, which contributes to the sustained fibrotic response. Therapeutic targeting of NADPH oxidase-4 (NOX4), a primary source of reactive oxygen species (ROS) in myofibroblasts, can inhibit fibrosis development and reverse established lung fibrosis. We sought to understand the role of cellular senescence and NOX4 activation and persistence of cardiac fibroblasts with progression to HF. Methods and Results: Mice carrying a mutation in the phospholamban gene (PLNR9C) develop progressive dilated cardiomyopathy (DCM), extensive cardiac fibrosis and HF. Using the Langendorff hanging heart method and flow cytometry, cardiac fibroblasts were isolated and studied for markers of cellular senescence. Cardiac fibroblasts from PLNR9C mice with DCM display a senescent phenotype, with significantly elevated levels of the senescence markers p16 (2.1-fold, p&lt;0.01, n=3, Figure) and beta-galactosidase (1.7-fold, p&lt;0.01, n=3), along with significantly increased ROS production (Amplex Red assay 2.5-fold, p&lt;0.01, n=3), as compared to fibroblasts from age-matched wild type (WT) mice. Nox4 is upregulated in cardiac fibroblasts from PLNR9C mice (mRNA 8.5-fold, n=4, p&lt;0.01; protein 5.0-fold, p&lt;0.01, n=4, Figure) with HF but not in young PLNR9C mice prior to development of DCM. Conclusions: These data reveal a premature aging phenotype in cardiac fibroblasts from mice with genetic DCM and identify NOX4 as a putative mediator of fibroblast activation and persistence.
Abstract 14440: Machine Learning-Based Approaches to Identify Diabetic Cardiomyopathy
Authors: Kershaw Patel, Matthew Segar, Muthiah Vaduganathan, Wai Hong W Tang, Duwayne Willett, Ambarish Pandey
Journal: Circulation (2022)

Introduction: Machine learning methodology can provide means for the identification of diabetic cardiomyopathy (DbCM), a severe and evolving complication of diabetes that leads to high morbidity and mortality. Phenotypic characterization of patient subgroups may support clinically relevant risk stratification in the population with DbCM. Methods: Among individuals with diabetes from the ARIC study cohort (training, n=953), unsupervised hierarchical clustering was performed with 24 candidate variables incorporating echocardiographic parameters, NT-proBNP, and hs-cTnT. The cluster with highest risk of HF was identified as DbCM. A deep learning (DL) classifier was developed to predict DbCM in the ARIC training cohort and validated in a pooled community-based cohort (ARIC testing plus CHS; n=1,050) and an electronic health record (EHR) cohort (n=3,139). Results: Clustering identified 3 phenogroups. Participants in group 3 (vs. 1 and 2) were more commonly men, had higher levels of creatinine, hs-cTnT, and NT-proBNP, higher LA size and LVMi, and increased prevalence of diastolic dysfunction and hypertension. The 5-year risk of HF was significantly higher in phenogroup 3 and thus identified DbCM (17.8% vs. 2.0% [phenogroup 2] vs. 3.5% [phenogroup 1]) ( Figure 1A ). The key predictors of DbCM were NTproBNP, LVMi, LA size, and diastolic dysfunction parameters ( Figure 1B ). The DL classifier demonstrated high model performance in identifying DbCM (AUROC = 0.96, accuracy = 0.93, and precision = 0.75). In the validation cohort (community-based), the DL classifier identified 16% of participants with DbCM with a two-fold higher risk of HF (HR [95% CI], 1.99 [1.47-2.67]; ref = no DbCM). A similar pattern of findings was observed in the EHR cohort (37% with DbCM; DbCM vs. no DbCM: HR [95% CI], 1.58 [1.17-2.12]). Conclusion: Machine learning-based techniques can be used to define and identify DbCM which is associated with higher risk of overt HF.